MELISA® Medica Foundation


4th International MELISA Study Group 24-27 July 1997 The 4th MELISA Study Group was arranged in the MELISA Medica Foundation building “Sjövillan“ situated at Danderyds Hospital in Stockholm.
The main theme for the seminar was the development and clinical use of newer diagnostic methods in patient groups with chronic illnesses related to metals, as well as reports of clinical trials to treat these patients. During four days participants from Austria, Germany, Italy, Switzerland and Sweden had opportunity to listen to lectures presented by Prof. Vera Stejskal, Karolinska Institutet in Stockholm, Antero Danersund, MD, Department of Clinical Metal Biology at University Hospital in Uppsala (Sweden), Romuald Hudecek, DDS, Department of Clinical Metal Biology at University Hospital in Uppsala, Biomedical Dental Centre in Uppsala and Melisa Medica Foudation (Sweden), Berit Thyberg-Persson, MD, Melisa Medica Foundation (Sweden), Johann Lechner, DDS, Vicepresident of GZM, University of Munich (Germany), Klas Runow, MD, President of Institut für Umweltkrankheiten in Emstal (Germany), Assoc. Prof. Ottaviano Tapparo, DDS, University of Constanza, and Munich (Germany) and Kurt Müller, MD, Isny (Germany). Extensive time was reserved for free discussion and additional shorter reports from the participants. Prof. Uno Svedin, MD, and research Secretary Vera Nováková, PhD, from the Swedish Council for Planning and Coordination of Research (Forskningsrådsnämnden, FRN) in Stockholm were invited guests. FRN is now in the process of examination of the newest scientific and clinical achievements in this field in order to produce a report for the Swedish Government about possible risks and safety matters of the use of dental amalgams. The seminar started with a “get together party“ in the evening of the 24th. Informal discussions gave a picture of similar problems in several countries, neglecting the risk of negative health effects related to various dental materials, especially metals and metal alloys. The ignorance of majority of the scientific community to recognize a near standing paradigm shift in the mercury/amalgam field, leads, according to several participating doctors experience, to a massive opposition against new research results and clinical case reports. In many cases, healthy scientific skepticism has been exchanged for total negativism in the matter of negative health changes due to the exposition of humans to the metals through dental materials. Some of participants described the situation as an “immature emotional reaction“ from many established experts in the main stream medicine, instead of more expected scientific curiosity about new research findings and clinical experience. The first working day of the seminar was opened by Prof. Vera Stejskal who welcomed all and gave a lecture about immunological principles in metal-protein-complex inducing activation of memory cells in human blood. She repeated shortly the metodology of MELISA® (Memory Lymphocyte Immuno Stimulation Assay) of the method in a study of 95 patients with Chronic Fatigue Syndrome (CFS) - like syndrom and 84 healthy subjects. The results of the study was recently presented at an international meeting regarding health effects of mercury at the Faroe islands. The control group has been biased by including only those subjects who claimed not being aware about hypersensitivity towards any metals. The sensitivity to metals is most probably directed by genetic constitution and that is why only certain individuals react with hypersensitivity reactions after sensitization and exposure to different metals. Also the degree or severity of the adverse reactions is depending more on individual sensitivity rather than upon the dose of exposition. That is why the classical design of a study with a homogenous group of patients and controls is less suitable in studies of individual sensitivity towards the metals. It is therefore not possible to match the patient group and the control group properly because the genetic factors are unexplored and unknown. The best way is to design a longitudinal study when the patients are monitored with biological markers (such as MELISA®) before and after a treatment and parallely eventual changes in patients health-condition are followed under a long time. In this actual group of patients, the lymphocyte reactivity to inorganic and organic mercurials was studied as well as the lymphocyte reactivity to other common metals such as gold and palladium. These metals belongs to the group of transition elements and are frequently used in dental restorations. It was found that lymphocyte reactivity to inorganic Hg, phenyl-Hg, Au and Pd was significantly higher in CFS-group than in healthy subjects (p<0,001 for inorganic Hg, Ph-Hg and Au; p<0,007 for Pd). Lymphocyte responses to Ni and other metals such as ethyl-Hg, Pb or Cd were similar in both groups. Upon the replacement of amalgams and other metal alloys, the patients experienced long-term health improvement. This clinical improvement correlated with the disappearance of metal sensitivity in MELISA®. The specificity and sensitivity of MELISA® were over 70%. Conclusion of this study was that mercurials and other metals used in dental restorations may induce systemic sensitization in susceptible individuals. Metal-induced chronic inflammation may adversely affect human health. Memory lymphocytes can be used as susceptibility markers for the diagnosis and proper medical and dental treatment of metal-sensitive patients. Wolfgang Mayer, representing Medicinisch Immunologische Laboratorien in Munich, presented data on frequencies of metal specific lymphocyte stimulation (MELISA®) in 1200 patients referred to the laboratory because of suspected metal intolerance. Their results corroborated the results from two independent Swedish MELISA®-laboratories in more than 2000 patients. Thus, the frequencies of positive MELISA® tests is highest with nickel, followed by inorganic Hg, gold, palladium and cadmium. Wolfgang Mayer presented also a comparison of results in two published studies on the use of epicutaneous patch test (EPT) in metal hypersensitivity. A Swedish study and a German study, showed very differing frequencies of metal sensitization in the patient materials which were supposed to be alike. This supports the widely spread opinion that EPT has low sensitivity in patient group claiming health problems due to exposure of metals from dental restorations. Dr. Antero Danersund presented a study on 25 patients with CFS-like clinical picture. This study (Ulf Lindh et al 1997, accepted for publication) is a part of a larger work evaluating development of new medical and odontological diagnostic and treatment methods at the Department of Clinical Metal Biology (Amalgamenheten) in University Hospital in Uppsala where about 1000 patients with suspected metal intolerance have been examined. Actual study shows the changes in intracellular content of trace elements, including mercury. The techniques used were Protone induced X-ray Emission (PIXE) and Inductively Coupled Plasma Mass Spectrometry (ICPMS). The patient group and control group differed significantly in PIXE results (p<0,001). After specific medical and dental treatment (controlled process of metal removal according to a special protocol) the new PIXE examination of blood cells was done as well as new ICPMS measurement of mercury content in erythrocytes and blood plasma. The intracellular content of trace elements has normalized and content of Hg in blood diminished even below the level in control group. All changes were statistically highly significant. This normalization in biomarkers was followed by significant reduction of patients health problems, both as individuals and as a group. Dr. Romuald Hudecek presented dental aspect for treating patients with dental material intolerance. The system was worked out at Biomedical Dental Centre in Uppsala together with Department of Clinical Metal Biology at University Hospital in Uppsala. Principles in all dental treatment in this special patient group are, accordingly known allergological and toxicological principles, to remove as completely as possible all substances which have been found to have negative health effects on a patients body. The replacement dental material has to be individually biocompatible. The removal has been to be carried out with extreme precautions in order to minimize involuntary increased exposition which is otherwise common in routine dental treatment. Special security equipment and working strategies were presented. Scanning Electron Microscope (SEM) pictures of air samples showed that precaution steps presented have minimized exposition for particles of dental material released by drilling. Especially amalgam particles and mercury vapor have been pointed out as not easy to be controlled because by drilling in amalgams a fraction of very small, invisible particles is released (0,1µ - 40µ). This fraction behaves as a gas, floating around in the working area, being potential health risk not only for the patients but also for dental personal. Measurements showed that it is possible to control and minimize the spread of unwanted material particles in the working area. Principles of construction of large ceramic bridges in In-Ceram® have been presented as they have been systematized at Biomedical Dental Centre. Clinical cases have been presented, showing good results with use of ceramic materials and individually chosen polymer materials. Dr. Christer Olsson, DDS, Biomedical Dental Centre in Uppsala, presented a clinical system of choosing individually biocompatible polymer materials as well as different cements in patients with multiple intolerance of dental materials. He pointed out that the detail knowledge about the composition of dental materials is of crucial importance when trying to avoid substances which the patient is allergic to. It is even important to control by chemical analysis the degree of pollutants (often metals) in composite materials because they are never declared by manufacturers. Composite materials with no or little content of coloring pigments (metal compounds) are recommended for use in sensitive patients. Prof. Tapparo informed that the Vivadent company in Lichtenstein will once again produce the composite material Heliomolar® in a special version without any color pigments. This material was earlier available only for a few dentists in Sweden and used with good clinical results in patients with intolerance against these substances (e.g. titanium dioxide). Prof. Ottavio Tapparo presented his study of jaw bone condition in about 2000 cases between 1989 - 1996. Bone lesions presented had defects in bone structure earlier classified in implantology as bone quality D4 in clinical cases with indication for surgical intervention due to pathological X-ray findings. All 2000 biopsies were analyzed with multiple element analysis and high content of metals such as mercury, cadmium, molybdenum, copper and tin were found. Content of these metals exceeded in 70 - 80 % of cases levels which are toxicologically considered as “normal“ in jaw bone The hypothesis was that most of this metal content has its origin in tooth fillings. After a period of time following the removal of all metallic dental restorations from the oral cavity new biopsies were taken and analyzed. The content of almost all metals decreased so that only about 10% of biopsies showed metal content exceeding the “normal“ levels. Many of bone lesions showed fatty degeneration as well as frequently aseptic necrosis. In cases of bacterial findings in these lesions a hypothesis of a secondary infection could be of plausibility. In presented appearance, described lesions could be in many cases recognized as Neuralgia Induced Cavitational Osteonecrosis (N.I.C.O.). The second working day of the seminar was opened by Dr. Johann Lechners lecture about jaw bone cavities and the connection of these with systemic health changes. Dr. Lechner discussed the term N.I.C.O. which is now widely known in USA and some countries in continental Europe. He was not very happy about the concentration on local pathological changes in jaw bone only, as it is described by Prof. Jerry Bouquot (USA). According to Dr. Lechner the terms which should be used is Chronic Cavitational Osteitis or Chronic Cavitational Osteonecrosis. These terms do not bind the pathologic lesion to only local process in the jaw bone. From clinical observations it is obvious that quite a number of symptoms distant from the jaws disappeared or diminished after a thorough surgical intervention in these cavities filled with necrotic bone. He presented statistics of 175 cases of the lesions and showed his system of clinical application of Electro-Acupuncture (Voll/VEGA), and Arm-length-reflex test. These diagnostic methods gave in presented 175 patients a fault frequency of only 5 cases. Doctor Lechner also presented a possible explanation of pure success to diagnose these bone cavities by X-ray. Multi-element analysis of bone necrosis showed that calcium and phosphate decrease dramatically and content of metals increases instead. This might be an explanation of “neutral“ X-ray performance. Dr. Lechner showed some clinical cases of pathologic bone cavities which were not possible to observe at X-ray but became elegantly visible by injection of contrast medium. Dr. Lechner pointed out that it is obvious that a chronic inflammation, lying directly on the nervous tissue (e.g. nervus mandibularis), with disintegration of the canalis mandibulae, will provoke massive disturbing impulses - transmitted by afferent fibres of the mandibulaar nerve. Such as extensive process as described is however usually not visible on X-ray, what was proven by his own Mass Spectrografic Test. In discussion with many questions after Dr. Lechners lecture it became clear that for instance in Austria, it is very little known about such pathological lesions as presented by Lechner and Tapparo. The same seems to be the fact in Sweden even though N.I.C.O. is since several years described in at least four major pathology text-books in USA. The question about frequency of such bone destruction in a population was answered by Dr. Lechner and Prof. Tapparo that these lesions seems to be “epidemic“ as soon as an experienced surgeon has learned to discover them. Anyhow, it seems not to be a very rare condition, especially not in the patients with chronic systemic inflammation. Dr. Hudecek reminded that the conditions for dental medicine are quite varying in different countries, even within EU. The use of so called “alternative medicine“ diagnostics and treatment methods is strongly dissaproved in Sweden by the National Board of Health and Welfare. Prof. Stejskal commented that we have to make strong efforts to test our hypotheses by scientifically accepted methodology because it will be the shortest way to have the health problems with metals in chronically ill subjects recognized. The scientific research will have stronger impact on conservative attitudes when an international cooperation corroborates the results between independent research centers and laboratories (e.g. actual cooperation between Melisa® laboratories in Germany and Sweden). Dr. K. E. Muller gave a summary in the latest achievements in neurological diagnostics of brain damage caused by xenobiotics. Exposure to neurotoxic chemicals such as pesticides, solvents and formaldehyde are known to induce neurologic and psychiatric symptomatology as well as metals. Besides sensible and motoric dysfunction, patients complained of vertigo, headache, lack of concentration, depression and loss of coordination. Concerning the last point neurological findings often are poor. Therefore in 64 patients (37 male, 27 female), the status of dopamine D2 receptors (D2R) of the basal ganglia was studied by single photon emission tomography (SPECT) using 185 MBq of Iodobenzamid (I-123-IBZM). 67% had a reduction of D2R at least on one side of the brain stem and showed a quotient (Q) below the critical mark of 1,40. Those, who had been exposed to dental metals, especially Hg, over long times, had the strongest affection on both sides of the basal ganglia. 50% of the pathological results were below Q=1,32, more than in any other group. Formaldehyde showed a similar pattern. However, the reduction of D2R was not as intensive. In a second study the regional cerebral blood flow had been examined by SPECT in 121 patients (55 male, 66 femare) using 450-550 MBQ of (technetium-99m) hexamethylpropyleneoxime (Tc-HMPAO). 83 patients had been exposed to Hg released from amalgam fillings. Only 13% (11 persons) out of this group showed a normal pattern of perfusion. Areas of hypoperfusion were more prevalent on the left than on the right side of the brain (relation 3:1). On both sides the temporal region was the most affected part, followed by the left frontal and the right occipital lobe. The evaluations of Kirkpatrick et al. might give an explanation for this phenomenon. He showed, that very low concentrations of metals induced the expression of cell adhesion molecules (CAMs), which are known as an essential component of endothelial inflammation and at least damage. These results should draw attention to possible effects of low concentrations of metals on the induction of hypoperfusion of the brain up to apoplectic insults, the induction of some forms of hypertension and vascular complications as purpura pigmentosa progressiva or Raynaud syndrome. The state of hypoperfusion of the brain cannot be demonstrated by magnetic resonance imaging (MRI) or computed tomography (CT). Dr Klas Runow presented a policy used in the Centrum for on Environmental Medicine, Bad Emstal. In the case of chronic diseases, pollution burdens and allergies have to be basically taken into account as triggers. Therefore, diagnosis in the field of environmental medicine has to be accepted as medically necessary, to be able to initiate an individual therapy, which is oriented to the triggers. Within the framework of diagnosis, environmental chemicals (pesticides, solvents) and also dental alloys are checked allergologically and toxicologically. The diagnostical and therapeutical procedure is summed up in the IFU (Institute for Environmental Medicine) guide of Environmental Medicine. Due to the increasing number of hypersensitive patients, even the hospitals have to adapt themselves more to these patients in the future. This is why practising environmental physicians and clinical ecologists demand, that the Hospital 2000 has to have an ecological department, which is constructed according to the IFU concept in an ecological way and where the staff is trained in the fields of allergology, toxicology and nutritional medicine. Dr. Berit Thyberg-Persson presented a way to investigate and treat patients with metal sensitivity, many of them also suffering from sensitivity to electricity, from the view of a general practitioner with a low budget and thereby without possibilities to use expensive but very direct tests like PIXE method. An allergy test like the MELISA test is most useful. Despite the low budget, it is important to do a thorough investigation to discover or exclude other serious illnesses before treating the patients with anti-oxidants. The choice of this special treatment is due to the fact that metals gives rise to free radicals like the oxygen we breathe and the stress all around us. Free radical causes illness. Metals can also cause illness by binding to sulphydryl groups in proteins all over the body and they can give rise to chronic inflammation. To protect and to heal patients from these damages requires lots of vitamins and certain minerals, that is anti-oxidants, some of them also functioning as chelators. Many of the symptoms these patients present are identical to symptoms of deficiency of these substanses and could in fact be due to them because of the increased need they experience. A list of some symptoms of deficiency and also toxic doses of these vitamins and minerals was presented. The third day of the Seminar was occupied by information and demonstrations of MELISA® technology. Prof. Stejskal explained and demonstrated the routine of defibrination of the blood sample. She informed about the new development of vacutainers which possibly will make it possible to send blood samples from abroad. Following a visit at the laboratory she gave the participants more information about MELISA®-tests performance such as double checking of the reliability of test results by microscopic morphology evaluation. The visitors attendance was also directed to the fact that MELISA® in not only suitable for discovering metal sensitization in human blood but also for sensitization to other low-molecular haptens such as drugs and possibly monomers and other compounds in composite materials.

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